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α2‐Adrenergic effect on human breast cancer MCF‐7 cells

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Abstract

(-)Epinephrine (Epi) and –Norepinephrine (NEpi) significantly stimulated tritiated Thymidine incorporation in MCF‐7 cells at concentrations 10–30 pM to 10 nM, with an EC50 of 10 pM for Epi and 14.2 pM for NEpi. To characterize this action, cells were incubated in the presence of NEpi or Epi and different antagonists. The β‐adrenergic antagonist Propanolol showed no effect on the agonist's stimulation, whereas the α‐adrenergic antagonist Phentolamine, reverted it completely at high concentrations (100 μM). The α1‐adrenergic antagonist Prazosin (Pra) acted only at high concentrations, while the α2‐adrenergic antagonist Yohimbine (Yo) reverted the stimulation at an EC50 of 0.11μM. Likewise, when the cells were incubated in the presence of the specific α2‐adrenergic agonist Clonidine (Clo), Thymidine incorporation was significantly stimulated at an EC50 of 0.298 pM. Again, the incubation of the cells in the presence of the α1‐adrenergic antagonist Pra exerted its action at high concentrations, whereas the α2‐adrenergic antagonist Yo showed a clear reversal of the agonist's enhancement at an EC50 of 0.136 μM.

Moreover, Clo caused a clear and significant inhibition of stimulated cAMP levels both in the intracellular and the extracellular fractions. Yo showed a complete reversion of cAMP levels to control values in the presence of Clo, while Pra had the opposite effect. These data suggest that the stimulation provoked in Thymidine incorporation by the agonists Epi, NEpi, and Clo is, at least in part, due to an α2‐adrenergic mechanism directly on tumoral cells, and that the effect is coupled with inhibition of cAMP levels, as described for this kind of receptors.

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Authors and Affiliations

  1. Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina

    Stella Maris Vázquez & Omar Pignataro

  2. Member of the Research Career of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina

    Isabel Alicia Luthy

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  1. Stella Maris Vázquez
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  2. Omar Pignataro
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  3. Isabel Alicia Luthy
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Vázquez, S.M., Pignataro, O. & Luthy, I.A. α2‐Adrenergic effect on human breast cancer MCF‐7 cells. Breast Cancer Res Treat 55, 41–49 (1999). https://doi.org/10.1023/A:1006196308001

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